Molecular mechanisms of homeostatic synaptic plasticity

What is it about?

Homeostasis is the maintenance of physiological variables within stable operational ranges in face of destabilizing stimuli through negative feedback mechanisms. Synaptic homeostasis, also known as synaptic scaling, refers to the feedback process operative at the neuronal synapse that maintains the strength of synaptic transmission within a dynamic range despite ongoing alterations in input activity. It is based on changes in the number of functional glutamate receptors, mainly the AMPA-type (AMPARs), that scales the synaptic output of excitatory synapses to compensate for prolonged changes in neuronal activity. This review article highlights the key molecular events that are involved in AMPAR regulation in synaptic homeostasis.

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Why is it important?

Synaptic homeostasis maintains neuronal excitability, too much or too little of which disrupts propagation of signal through the network and impairs brain function. Brain function relies on balance between excitation and inhibition (E/I balance) in the neuronal networks. Our life experiences as we interact with our environment tend to shift this balance away from equilibrium and in extreme cases can drive the brain towards overexcited states, such as epileptic seizures or a quiescent state, such as coma. Dysfunction in E/I balance is associated with several neurological disorders such as autism, schizophrenia as well as Alzheimer, Huntington’s disease. Synaptic homeostasis preserves E/I balance and understanding its mechanisms will help design effective strategies fulfilling unmet therapeutic needs.

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